Clinical associations of complement-activating collectins, collectin-10, collectin-11 and mannose-binding lectin in preterm neonates.

Introduction: Premature and low-birthweight infants are at especially high risk of perinatal complications, including impaired thermoregulation, infections and respiratory distress. Such adverse effects and the need for invasive procedures are associated with high mortality among preterms. This study focused on the influence of the innate immune system and tested the levels of collectins, collectin-10 (CL-10), collectin-11 (CL-11) and mannose-binding lectin (MBL) in preterm neonates.

MASP-2 deficiency does not prevent the progression of diabetic kidney disease in a mouse model of type 1 diabetes.

Mannan-binding lectin (MBL) initiates the lectin pathway of complement and has been linked to albuminuria and mortality in diabetes. We hypothesize that MBL-associated serine protease 2 (MASP-2) deficiency will protect against diabetes-induced kidney damage. Male C57BL/6J MASP-2 knockout (Masp2) mice and wildtype (WT) mice were divided into a diabetic group and a non-diabetic group.

Mannan-Binding Lectin Is Associated with Inflammation and Kidney Damage in a Mouse Model of Type 2 Diabetes.

Autoreactivity of the complement system may escalate the development of diabetic nephropathy. We used the BTBR OB mouse model of type 2 diabetes to investigate the role of the complement factor mannan-binding lectin (MBL) in diabetic nephropathy. Female BTBR OB mice ( = 30) and BTBR non-diabetic WT mice ( = 30) were included.

Development of an immunoassay for quantification of soluble human CD40L (CD154) in plasma and serum samples.

When the membrane protein CD40 ligand (CD40L) on activated T cells binds the receptor CD40 on B-cells, it provides a co-stimulatory signal for B cell activation. Dysregulation of the CD40L:CD40 axis is associated with inflammatory and autoimmune diseases. The presence of soluble CD40L (sCD40L) in plasma is implicated in several diseases, from cardiovascular and autoimmune diseases to different types of cancer, and sCD40L has been suggested as a valuable marker of disease.

Inter-α-trypsin inhibitor heavy chain 4 (ITIH4) as a compensatory protease inhibitor in hereditary angioedema.

Background: Hereditary angioedema (HAE) is a genetic disorder that manifests as recurrent angioedema attacks, most frequently due to absent or reduced C1 inhibitor (C1INH) activity. C1INH is a crucial regulator of enzymatic cascades in the complement, fibrinolytic, and contact systems. Inter-α-trypsin inhibitor heavy chain 4 (ITIH4) is an abundant plasma protease inhibitor that can inhibit enzymes in the proteolytic pathways associated with HAE.

Diagnostic and prognostic value of mannan-binding lectin associated protein (MAp19) for functionally relevant coronary artery disease.

Background: This study aimed to evaluate the diagnostic and prognostic potential of MAp19, a regulating component of the lectin pathway of the complement system, in patients with suspected functionally relevant coronary artery disease (fCAD) as well as the determinants of MAp19 levels.

Methods: The presence of fCAD was adjudicated using myocardial perfusion imaging with single-photon emission tomography and, where available, coronary angiography. MAp19 levels were measured in participants at rest, at peak stress tests, and two hours after the stress.

Effect of dapagliflozin on collectins and complement activation in plasma from patients with type 2 diabetes and albuminuria: Data from the DapKid cohort.

Background: Sodium-glucose cotransporter 2 (SGLT- 2) inhibitors exert cardiovascular and kidney-protective effects in people with diabetes. Attenuation of inflammation could be important for systemic protection. The lectin pathway of complement system activation is linked to diabetic nephropathy.

Diagnostic and prognostic value of H-ficolin for functionally relevant coronary artery disease.

Background: We aimed to test the diagnostic and prognostic ability of H-ficolin, an initiator of the lectin pathway of the complement system, for functionally relevant coronary artery disease (fCAD), and explore its determinants.

Methods: The presence of fCAD was adjudicated using myocardial perfusion imaging single-photon emission tomography and coronary angiography. H-ficolin levels were measured by a sandwich-type immunoassay at rest, peak stress-test, and 2 h after stress-test.

An integrated organoid omics map extends modeling potential of kidney disease.

Kidney organoids are a promising model to study kidney disease, but their use is constrained by limited knowledge of their functional protein expression profile. Here, we define the organoid proteome and transcriptome trajectories over culture duration and upon exposure to TNFα, a cytokine stressor. Older organoids increase deposition of extracellular matrix but decrease expression of glomerular proteins.

Differentiating between activation via the lectin or the classical complement pathway in patients with systemic lupus erythematosus.

Complement activation is a hallmark of systemic lupus erythematosus (SLE) and can proceed through the classical (CP), lectin (LP), or alternative pathway (AP). When managing SLE patients, pathway-specific complement activation is rarely monitored as clinical assays are unavailable. In this study, we aim to differentiate between CP- or LP-mediated complement activation in SLE patients by quantifying pathway-specific protein complexes, namely C1s/C1-inhibitor (C1-INH) (CP-specific activation) and MASP-1/C1-INH (LP-specific activation).

Platelets and the Lectin Pathway of Complement Activation in Patients with Systemic Lupus Erythematosus or Antiphospholipid Syndrome.

 Patients with systemic lupus erythematosus (SLE) have an increased risk of thrombosis even when they do not have antiphospholipid syndrome (APS). Interactions between complement activation and activated platelets have been suggested in SLE and APS and could play a role in the increased thrombosis risk.  To explore factors potentially related to the prothrombotic pathophysiology in patients with SLE, primary APS, and healthy controls, by investigating lectin pathway proteins (LPPs), complement activation, platelet aggregation, and platelet activation.

Restriction of C1-inhibitor activity in hereditary angioedema by dominant-negative effects of disease-associated SERPING1 gene variants.

Background: Patients with hereditary angioedema experience recurrent, sometimes life-threatening, attacks of edema. It is a rare genetic disorder characterized by genetic and clinical heterogenicity. Most cases are caused by genetic variants in the SERPING1 gene leading to plasma deficiency of the encoded protein C1 inhibitor (C1INH).

Inter-α-inhibitor heavy chain H4 and sepsis-related coagulation disturbances: Another link between innate immunity and coagulation.

Background: The protease inhibitor inter-α-inhibitor heavy chain H4 (ITIH4) has been described as an acute-phase reactant and could potentially aid in sepsis monitoring and prognostication.

Objectives: To investigate ITIH4 plasma levels in sepsis patients compared with healthy controls and to examine the association between ITIH4 and acute-phase response markers, blood coagulation, and organ dysfunction in sepsis.

Methods: We performed a post hoc study to a prospective cohort study.

Antigen footprint governs activation of the B cell receptor.

Antigen binding by B cell receptors (BCR) on cognate B cells elicits a response that eventually leads to production of antibodies. However, it is unclear what the distribution of BCRs is on the naïve B cell and how antigen binding triggers the first step in BCR signaling. Using DNA-PAINT super-resolution microscopy, we find that most BCRs are present as monomers, dimers, or loosely associated clusters on resting B cells, with a nearest-neighbor inter-Fab distance of 20-30 nm.

Highly Increased Levels of Inter-α-inhibitor Heavy Chain 4 (ITIH4) in Autoimmune Cholestatic Liver Diseases.

Background And Aims: There is an unmet need for new biomarkers to improve diagnostics and prognostics in primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC). Inter-α-inhibitor heavy chain 4 (ITIH4) is an abundant, liver-produced protein, and its synthesis may be altered in liver diseases. We investigated whether ITIH4 plasma concentrations were affected in PBC and PSC patients.

Mannan-binding lectin serine protease-2 (MASP-2) in human kidney and its relevance for proteolytic activation of the epithelial sodium channel.

Proteolytic activation of the renal epithelial sodium channel (ENaC) is increased by aldosterone. The aldosterone-sensitive protease remains unidentified. In humans, elevated circulating aldosterone is associated with increased urinary extracellular vesicle (uEVs) excretion of mannan-binding lectin associated serine protease-2 (MASP-2).

A low level of naturally occurring antibodies associates with functional antibody deficiency.

Functional antibody deficiency is clinically assessed from antibody responses to vaccination. However, diagnostic vaccination is complex and may fail in practice. We hypothesized that the levels of naturally occurring antibodies against galactose-α-1,3-galactose (αGal) may represent alternative markers of functional antibody capacity.